Patent RU-2747260-C2 (RU)
Title: Rfrf4 inhibitor, method of its preparation and its pharmaceutical application
Inventor: YANG FEI
IPC: C07D471/04
Filed: 2017-12-14
Granted: 2021-04-29
Abstract: FIELD: organic chemistry.SUBSTANCE: invention relates to the field of organic chemistry, namely to a compound of formula (IVa-1), its stereoisomer or a pharmaceutically acceptable salt in which X1 is —CH— or N; Z representsor; R2, R3, R4and R5are selected from H, Cl, F, methyl, isopropyl, cyclopropyl, and —O — R11; R8is selected from H, halogen, unsubstituted or substituted C1-5alkyl, C3cycloalkyl, unsubstituted or substituted 6-membered heterocyclyl selected from tetrahydropyran, piperidine, dihydropyran, C6aryl, unsubstituted or substituted 5-6 membered heteroaryl, selected from pyridine and pyrazole, -C0-2-O-R11and -C0-2-NR13R14, said alkyl, heterocyclyl and heteroaryl are unsubstituted or substituted with 1-3 substituents selected from unsubstituted or substituted C1-alkyl, C1-haloalkyl, C3cycloalkyl, unsubstituted or substituted 5-membered heterocyclyl selected from tetrahydrofuran and pyrrolidine, C6aryl, unsubstituted or substituted 5-membered heteroaryl selected from pyrazole, and —C2 — O— R11, wherein said alkyl, heterocycle and heteroaryl are unsubstituted or substituted with one substituent selected from C1-alkyl and C3-cycloalkyl; R11is selected from H, C1-3alkyl optionally substituted with 1-3 substituents selected from deuterium and C3cycloalkyl, and C6aryl substituted with two C1alkoxy substituents; R13and R14are selected from H, unsubstituted or substituted C1-6alkyl, unsubstituted or substituted C3-5cycloalkyl, unsubstituted or substituted 4-6-membered heterocyclyl selected from oxetane, tetrahydrofuran, tetrahydropyran, pyrrolidine, azetidine and piperidine, C6-aryl and C1-3-alkylsulfonyl or R13and R14, together with the nitrogen atoms to which they are directly bonded, form a 4-9-membered heterocyclyl selected from azetidine, pyrrolidine, morpholine, piperidine, 2-oxa-6-azaspiro [3 , 3] heptane, 1-oxa-6-azaspiro [3.3] heptane, 2-azaspiro [3.3] heptane, 6-oxa-2-azaspiro [3.4] octane, 2-azaspiro [3.4 ] octane, 7-oxa-2-azaspiro [3,5] nonane, 3-azabicyclo [3.1.0] hexane, 2-oxa-7-azaspiro [4.4] nonane, 6-oxa-3-azabicyclo [3.1 .1] heptane, 2-oxa-5-azabicyclo [2.2.1] heptane, said alkyl, cycloalkyl, heterocyclyl may be optionally substituted with 1-3 substituents selected from deuterium, cyano, halogen, C1-alkyl, unsubstituted or substituted C12-alkoxy, C1-3-alkylthio, C3-5-cycloalkyl, non-meth substituted or substituted 3-10-membered heterocyclyl, unsubstituted or substituted C6-aryl, substituted 5-membered heteroaryl selected from pyrazole, C1-2-alkylsulfonyl, C1-alkylsulfonylamino, mono-C1-3-alkylamino, di-C1- 3-alkylamino or hydroxyl; where said alkyl, alkoxy, heterocyclyl, heteroaryl and aryl are unsubstituted or substituted with 1-3 substituents selected from halogen, amino, C1-alkyl, C1-alkoxy, hydroxy, C1-alkoxyC2-alkyl, hydroxyC1-2-alkyl, or di -C1-3-alkylamino; unless otherwise indicated, said "heterocyclyl", "heterocyclyloxy", "heteroaryl" and "heteroaryloxy" have 1 to 2 heteroatoms selected from N, O or S. The invention also relates to a method for preparing a compound of formula (IVa-1), a pharmaceutical composition based on a compound of formula (IVa-1), the use of the composition and a compound of formula (IVa-1), a method for treating cancer and a method for inhibiting RFRF4.EFFECT: new heterocyclic compounds that inhibit the activity of RFRF4 kinase.14 cl, 1 tbl, 806 ex